P53-tumor suppressor gene overexpression in human papilloma virus-infected patients with oral squamous cell carcinoma

Abstract

Background: Via molecular DNA hybridization, more than 120 different genotypes of human papilloma virus havebeen confirmed. Many studies have described an association of high risk-HPV genotypes and overexpression ofmutated P53 gene with a variety of oral benign tumors as well as malignant squamous cell carcinomas. This studyaimed to: 1) Determine the prevalence of HPV DNA in archival tissue specimens with a range from apparentlyhealthy tissue to invasive oral S.C.C by using one of the recent versions of insitu hybridaization. 2) Define thegenotypes of the obtained HPV and to find out rational significance and relation of such genotypes to the severity ofunderlying lesions. 3) Study the correlation of over expressed products of mutant p53 genes with HPV-negative andHPV-related oral cancers.Materials and methods: A total number of 72 tissue specimens were collected from 41 patients with oral squamouscell (OSCC) and 31 individuals with apparently-healthy oral tissues (AHOT). The molecular detection methods for HPVdetection and genotyping were performed by in situ hybridization using cocktailed- and specified high- risk HPV DNAprobes, respectively. Immunohistochemical method was used to demonstrate the prevalence of P53 overexpressionin those oral cancers.Results: Among oral OSCC group, 16 archived tissue blocks were found to contain HPV DNA related to thecocktailed HPV genotypes. This result constituted 39% of the total oral SCC screened for HPV DNA. HPV-18 positiveoral SCC tissue blocks constituted (68.75%) whereas HPV genotypes 16& 31/33 constituted (43.75%) & (12.5%),respectively. Mixed infection of HPV genotypes was found in 31.3%. Interestingly, HPV DNA detection wasdocumented in 3.2% of those appeared as healthy tissues on histopathological examinations. Among oral SCCgroup, 22(53.7%) showed over expression of P53 tumor suppression gene. Interestingly, the co-occurrence of mutatedP53 overexpression and high oncogenic risk HPV genotypes was documented in 75% of Iraqi patients with OSCC.Conclusions: The significant prevalence of high oncogenic HPV genotypes detection in those patients with OSCCindicates a herald marks for the spread of such important sexually transmitted infection among Iraqi generalpopulation. Both of mutated p53 genes as well as high-oncogenic risk HPV genotypes could play an important role inoral carcinogenesis.